Changes in plasma membrane dynamics of liver cells following administration of a hepatotoxic agent activated by the liver endoplasmic reticulum is the major focus of this investigation. Dimethylnitrosamine has been selected as a representative toxic agent for this study. The hypothesis that at some point there is critical injury to the liver cell plasma membrane that triggers an uncontrolled calcium influx which may lead to cell death will be examined. The toxic agent will be administered to rats in vivo and will be added to incubating hepatocytes. Microviscosity, phospholipids and pumps of the membrane play a role in the control of calcium ion movements into the cell. This investigation will measure effects of toxic agents on these parameters at various times after administration of the agent in vivo or after addition of the agent to hepatocytes. The following are some of the parameters which will be studied: membrane micro-viscosity employing diphenylhexatriene and polarized fluorescence, phospholipid methyltransferase-a membrane activity which rapidly regulates microviscosity, cellular calcium homeostasis, calmodulin-the calcium regulator protein and calcium sequestering pumps of the endoplasmic reticulum. Dimethylnitrosamine will be compared with carbon tetracholoride, an agent activated by the endoplasmic reticulum which strongly modifies calcium regulation in the hepatic cell. Agents which may modify membrane microviscosity or calcium influx will be studied for their effects in minimizing membrane perturbations by toxic agents. A significant objective of this study is to examine the plasma membrane, a potentially critical site vulnerable to hepatic cell injury, for possible ways to protect the cell and minimize damage following exposure to toxic agents. Findings may be applicable to liver injury problems from causes other than the toxic agents under study.